A rhetorical question used when one is in a difficult predicament and the circumstances suddenly change in his/her favor, such as when the person in trouble pulls out a gat or when his/her posse shows up ready to whoop some ass. Often followed by "bitch" or "punk" to further assert dominance.

Barack Obama: "Now that I've won the Iowa caucus, I have the Democratic nomination in the bag. The New Hampshire primary is going to be a walk in the park."
(Hillary Clinton wins New Hampshire primary)
Hillary Clinton: "Hell yeah! What's up now, bitch???"
(Barack Obama wins the Democratic nomination)
Hillary Clinton (obviously insincerely): "Congratulations, Senator Obama. I am so happy for you. The American people definitely made the right choice."
Barack Obama: "Three words, Senator Clinton: WHAT'S UP NOW?!?!?!"